Intravenous Immunoglobulin Plus Methylprednisolone Mitigate Respiratory Morbidity in Coronavirus Disease 2019

• Published in: Critical care explorations 2020-11, Vol.2 (11), p.e0280
• Main Authors: Sakoulas, George, Geriak, Matthew, Kullar, Ravina, Greenwood, Kristina L, Habib, MacKenzie, Vyas, Anuja, Ghafourian, Mitra, Dintyala, Venkata Naga Kiran, Haddad, Fadi
• Format: Article
• Language: English
• Subjects: Original Clinical Report
• ISSN: 2639-8028; 2639-8028
• DOI: 10.1097/CCE.0000000000000280

Dysregulated neutrophil and platelet interactions mediate immunothrombosis and cause lung injury in coronavirus disease 2019. IV immunoglobulin modulates neutrophil activation through FcγRIII binding. We hypothesized that early therapy with IV immunoglobulin would abrogate immunothrombosis and improve oxygenation and reduce progression to mechanical ventilation in coronavirus disease 2019 pneumonia. Prospective randomized open label. Inpatient hospital. Hypoxic subjects with coronavirus disease 2019 pneumonia were randomized 1:1 to receive standard of care plus IV immunoglobulin 0.5 g/kg/d with methylprednisolone 40 mg 30 minutes before infusion for 3 days versus standard of care alone. Sixteen subjects received IV immunoglobulin and 17 standard of care. Median ages were 51 and 58 years for standard of care and IV immunoglobulin, respectively. Acute Physiology and Chronic Health Evaluation II and Charlson comorbidity scores were similar for IV immunoglobulin and standard of care. Seven standard of care versus two IV immunoglobulin subjects required mechanical ventilation ( = 0.12, Fisher exact test). Among subjects with A-a gradient of greater than 200 mm Hg at enrollment, the IV immunoglobulin group showed: 1) a lower rate of progression to requiring mechanical ventilation (2/14 vs 7/12, = 0.038 Fisher exact test), 2) shorter median hospital length of stay (11 vs 19 d, = 0.01 Mann Whitney test), 3) shorter median ICU stay (2.5 vs 12.5 d, = 0.006 Mann Whitey test), and 4) greater improvement in Pao /Fio at 7 days (median [range] change from time of enrollment +131 [+35 to +330] vs +44·5 [-115 to +157], = 0.01, Mann Whitney test) than standard of care. Pao /Fio improvement at day 7 was significantly less for the standard of care patients who received glucocorticoid therapy than those in the IV immunoglobulin arm ( = 0.0057, Mann Whiney test). This pilot study showed that IV immunoglobulin significantly improved hypoxia and reduced hospital length of stay and progression to mechanical ventilation in coronavirus disease 2019 patients with A-a gradient greater than 200 mm Hg. A phase 3 multicenter randomized double-blinded clinical trial is under way to validate these findings.